Download Ashkenazi Jewish Comprehensive Carrier Screening

Department of Human Genetics
Division of Medical Genetics
www.genetics.emory.edu
Ashkenazi Jewish Comprehensive Carrier Screening
(Tay Sachs, Canavan Disease, Familial Dysautonomia, Cystic Fibrosis, Bloom, Fanconi Anemia,
Gaucher, Mucolopidosis IV, Niemann Pick A)
©2008 All rights reserved.
Ashkenazi Ancestry: Having relatives from Eastern or Central Europe who practiced the Jewish faith, regardless of an
individual’s current religion or residence.
Sephardic Ancestry: Having relatives from Mediterranean areas (Greece, Spain, etc.) who practiced the Jewish faith,
regardless of an individual’s current religion or residence.
Autosomal Recessive (AR): A genetic condition caused by inheritance of an abnormal gene from two carrier parents.
The chance of an affected child is 1 in 4 or 25% for each pregnancy of two carrier parents.
Inheritance: All of the conditions included in this screening panel are inherited in an autosomal recessive manner.
The following conditions are more prevalent among individuals of Ashkenazi Jewish ancestry than in the general
population:
Tay Sachs Disease is fatal in children (usually by age 5) and involves progressive degeneration of the central nervous
system. Absence of an enzyme called hexosaminidase A (or hex A) causes a fatty substance to build up in the brain and
spine. The process begins in the fetus prenatally, but is not evident until the child is several months old. To date, there is
no cure for Tay Sachs disease.
Canavan Disease is similar to Tay Sachs in that it also involves progressive degeneration of the central nervous system
and is fatal in early childhood. The condition is caused by the absence of an enzyme called aspartoacylase (ASPA). To
date there is no cure for Canavan disease.
Familial Dysautonomia (FD) is a rare genetic condition involving deficiency of the enzyme beta hydroxylase. The
sensory and autonomic nerves (those controlling involuntary functions) are affected, resulting in problems with blood
pressure control, temperature regulation, feeding, growth, sensitivity to pain, and others. Early diagnosis and treatment
improves prognosis and survival, but there is no cure for the disease.
Cystic Fibrosis (CF) is a condition with a range of clinical severity. People with classic CF secrete abnormally thick body
fluids, especially in their lungs. The mucus interferes with normal body functions and leads to chronic infections. Classic
CF also involves the pancreas, resulting in decreased absorption of nutrients. Survival rates have improved, but death
ultimately occurs from respiratory failure. Some variant forms of CF may have only lung involvement, pancreatitis,
sinusitis, or infertility.
Bloom syndrome is caused by a gene defect that results in an increased number of chromosomal breaks. Affected
persons generally have short stature, skin color changes and rashes (especially after sunlight exposure), and increased
susceptibility to infections and cancer. Mental retardation occurs in some affected individuals. Fertility problems are
common in both sexes. While there is no cure for Bloom syndrome, treatment is geared toward prevention of symptoms.
Fanconi anemia, type C is also caused by a gene defect that results in an increased number of chromosomal breaks.
This leads to decreased production of blood cells, skeletal abnormalities, and an increased risk of cancer. Onset is
usually in childhood, with survival into the late teens or early twenties. Mental retardation, gastrointestinal problems and
cardiac abnormalities are seen in some affected individuals. In rare cases, diagnosis is in adulthood, generally because of
atypical cancers. Treatment is primarily preventative and includes frequent screenings and avoidance of the sun and
agents that cause chromosomal damage.
Gaucher disease, Type 1 is caused by deficiency of the enzyme glucocerebrosidase which results in storage of a fatty
substance called glucocerebroside in the spleen, liver, bone marrow and other systems. Onset may be early in life or
delayed until adulthood. Symptoms include easy bruising and bleeding, anemia, chronic fatigue, liver and spleen
enlargement, bone pain and bone fractures. Highly effective enzyme replacement therapy is available, but there is no
cure at this time.
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Mucolipidosis, type IV (ML4) is caused by a gene defect that leads to abnormalities of the nervous system and the eyes.
The earliest sign of ML4 may be clouding of the corneas in the first year of life, along with delayed motor milestones,
mental retardation and slowly progressive neurological deterioration. Affected persons have lived into their mid 40s.
Treatment includes supportive care, such as occupational or physical therapy. There is no cure for ML4.
Niemann Pick Disease, type A is caused by lack of the enzyme acid sphingomylinase (ASM), resulting in accumulation
of a fatty substance called sphingomyelin, and leading to severe damage to the central nervous system, liver, and lungs.
Symptoms beginning in infancy include loss of previously achieved milestones, blindness, progressive spasticity,
enlargement of the liver and spleen, and a “cherry red spot” in the back of the eye. There is currently no cure, and death
usually occurs by age 2-3.
Disease
Tay Sachs
Gene/Enzyme
Hex A
Hexosaminidase A
Carrier Rate
1 in 30 Ashkenazi
Methodology
Analysis for 7
1 in 30 French
common gene
Canadian/Cajun
mutations
Detection Rate
Over 92%
1 in 300 other ancestries
Canavan
Disease
ASPA
Aspartoacylase
1 in 36 Ashkenazi
Analysis for 4
1 in 360 other ancestries
common gene
Over 98%
mutations
Familial
Dysautonomia
IKBKAP
Beta-hydroxylase
1 in 30 Ashkenazi
Analysis for 2
Over 99%
common gene
mutations
Cystic Fibrosis
Bloom
syndrome
CFTR
CF Transmembrane
Conductance
Regulator
BLM
1 in 29 Ashkenazi
Analysis for 32
94% Ashkenazi
1 in 29 Caucasians
common gene
88% Caucasians
1 in 46 Hispanics
mutations
72% Hispanics
1 in 60-65 African Americans
65% African Americans
1 in 90 Asians
49% Asians
1 in 100 Ashkenazi
Analysis for 1
Over 97%
common gene
mutation
Fanconi
Anemia,
type C
FANCC
1 in 89 Ashkenazi
Analysis for 2
common gene
mutations
Over 99%
Gaucher,
type1
GBA
1 in 15 Ashkenazi
Analysis for 8
Over 97%
common gene
Glucocerebrosidase
mutations
Mucolipidosis,
type IV
MCOLN1
1 in 127 Ashkenazi
Analysis for 2
Over 96%
common gene
Mucolipin 1
mutations
Niemann Pick,
type A
ASM
Spingomylinase
1 in 90 Ashkenazi
Analysis for 4
Over 95%
common gene
mutations
If you have any questions about this information, please call Emory Genetics at 1-800-366-1502 and ask to speak with the
Genetic Counselor on-call.
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